tbuckley/cabot-search huggingface dataset:
Improving multidisciplinary patient-centered care for adolescents and young adults with cancer.
Authors: Leighton Andrew Elliott, Joanne P. Lagmay, Daimian Holiday Scott, Lauren Staley
Journal: Journal of Clinical Oncology (2023)

e13503 Background: Approximately 90,000 adolescents and young adults (AYA) are diagnosed with cancer annually. Poor outcomes are associated with decreased access to specialized care, limited opportunities for clinical trial participation, treatment protocol variations, and limited psychosocial resources. Fortunately, there has been an increased awareness of the unique challenges faced by AYA patients with the establishment of AYA programs around the world. In order to maximize management opportunities for this marginalized population, our academic healthcare system embarked to establish an effective AYA Oncology Program to serve within the continuum of Pediatric and Medical Oncology and survivorship. Herein, we report the outcomes from this important quality improvement initiative. Methods: In May 2018, the AYA program was established within Pediatric Oncology. We were able to hire a dedicated social worker in March 2020. At this time, growth of the program was limited due to the COVID pandemic. In January 2021, the consult order was updated to enhance tracking metrics. We aimed to increase AYA program consult orders by 20% from 2021 to 2022. In June 2021, we presented the AYA program to Medical Oncology and Malignant Hematology to increase program awareness. We implemented several other educational activities with the Department of Pediatrics, Department of Medicine (including Medical Oncology and Malignant Hematology), and the community via multiple Plan-Do-Study-Act (PDSA) cycles. Results: Since 2020, the AYA program has tracked 91 answered consults – 86 in the last 2 years. In 2022, there were 50 total consults placed compared to 36 in 2021, a 38.9% increase. Since 2021, the AYA program was consulted on 17.2% of newly diagnosed AYA patients. Inpatient consults were more common at 62.6%. Thirteen total consults were ordered for patients ≥30yo, of which only 2 were for patients older than 32. The AYA program was consulted on only 3.5% of newly diagnosed adults ≥30yo compared to 28.7% for the younger AYA patients. Upon surveying medical oncologists at our institution, most providers simply forget to order consults to the AYA program. Conclusions: Total AYA program consult numbers are increasing, however, there is opportunity for growth, especially in reaching the older AYA patients. Our healthcare system has recently approved the establishment of a Best Practice Advisory (BPA) in our electronic medical record to remind providers to order AYA program consults, if appropriate. Once the BPA is established, subsequent PDSA cycles will emphasize reaching older AYA patients by re-circulating educational resources and activities to providers and social workers in Medical Oncology and Malignant Hematology. Future objectives will evaluate outcomes in quality of life, overall survival, healthcare utilization, and clinical trial enrollment amongst other metrics.
Detection of methylation-based prognostic signatures in liquid biopsy specimens from patients with meningiomas.
Authors: Grayson Herrgott, James Snyder, Ana Valeria Castro, Houtan A. Noushmehr
Journal: Journal of Clinical Oncology (2023)

2073 Background: Detection of distinct epigenetic biomarkers in circulating cell-free DNA (cfDNA) of liquid biopsy (LB) specimens (e.g. blood) fosters opportunity for prognostication of central nervous system (CNS) tumors and has not been thoroughly explored in patients with meningiomas. Methods: We profiled the cfDNA methylome (EPIC array) in serum from patients with meningiomas (MNG; n = 93) and harnessed internal and external meningioma tissue methylome data with reported follow up (n = 77). To predict recurrence risk (RR), we consolidated a tissue cohort with at least 5 years of follow up and divided them into confirmed recurrence (CR; either reported progressive disease in post-surgical imaging, or additional resections following initial surgery) and confirmed no-recurrence (CNR: no confirmed disease progression w/in at least 5-years of follow-up). Then through application of an iterative process consisting of multiple tissue- and serum-based supervised analyses, we identified risk-specific methylation markers with potential for serum application. which, when inputted into a random forest algorithm allowed for segregation of both tumor tissue and liquid biopsy specimens according to recurrence risk. We estimated immune cell composition using MethylCIBERSORT, where a reference methylome atlas of chosen immune cell types was utilized to deconvolute the MNG samples. Results: The resulting recurrence risk classifier demonstrated an appreciable predictive power in classifying samples as high or low recurrence risk across the tumor tissue cohort (ACC: 87.7%, CUI+: 86.4%). When compared to another classifier of rivaling purpose, our model demonstrated statistically significant agreement across primary meningioma samples (κ = 0.269, p = 0.01), and more accurately predicted samples to recur across expanded time windows (time to recurrence &gt; 5 yrs). Across resulting liquid biopsy classifications, recurrence risk subgroups were analogous with reported risk factors, including WHO grade, extent of resection, and tumor location. Recurrence risk subgroups also demonstrated differential estimated immune cell contributions, with low-risk samples exhibiting a “hot” profile, or enrichment of B-Cells, CD56- and CD4 T-Cells, and natural killer cells. Notably, the estimated neutrophil to lymphocyte ratio, previously purported to be relevant to tumor prognosis, was appreciably higher for those meningioma samples with the highest recurrence risk. Conclusions: DNA methylation markers identified in the serum are suitable for the development of machine learning-based models which present high predictive power to prognosticate patients with meningioma and estimate a differential immune profile across recurrence risk groups. After validation in an external cohort, this noninvasive approach may improve the presurgical therapeutic management of patients with meningiomas.
Progress report of a cross-organ and biomarker-based platform study: BELIEVE trial NCCH1901.
Authors: Yayoi Ando, Tatsunori Shimoi, Kuniko Sunami, Natsuko Tsuda Okita, Mikio Mori, Taro Shibata, Kenichi Nakamura, Noboru Yamamoto
Journal: Journal of Clinical Oncology (2023)

TPS1611 Background: Cancer Genomic Medicine (CGM) has been developing and more patients have received the comprehensive genomic profiling (GCP) test under national healthcare system in Japan. However, the number of patients who could receive the genomically matched therapy based on the results of CGP tests was limited. To improve the drug accessibility, we initiated a cross-organ, biomarker-based clinical trial (NCCH1901, the BELIEVE trial). It was a platform trial and could be considered as the Japanese counterpart to the National Cancer Institute's Molecular Analysis for Therapy Choice (NCI-MATCH) study in the United States. Methods: It was a multi-institutional joint research nationwide led by NCCH with a master’s protocol. Several drug cohorts were pre-established, allowing patients to participate in molecularly targeted treatments recommended as a result of CGP test. All drugs were provided for free from the pharmaceutical companies. The objective of this trial was to administer off-label drugs for the respective genomic abnormalities and collect efficacy and safety data for patients of the drugs. The primary endpoint was the response rate based on the best overall response for up to 16 weeks. This trial has been conducted under both of the Japanese Clinical Trial Act and the patient-proposed healthcare services which enable patients to receive unapproved, off-label drugs partially covered by National Health Insurance. The protocol and the informed consent forms were approved by the National Cancer Center Hospital (NCCH) certified review board and the Ministry of Health, Labour and Welfare (MHLW). The trial was registered in the Japan Registry of Clinical Trials (jRCTs031190104). As of January 31, 2023, we have 20 drug cohorts and the planned number of enrollments for each cohort was 50 with the target lesions and 30 without the target lesions. There were more than 500 patients so far. The most common cancer was brain tumours, followed by carcinoma of endocrine organs and the colorectal cancer. BRAF mutation and ERBB2 amplification were the frequent genomic abnormalities registered in this trial. Five drug cohorts have already finished recruiting and 2 drug cohorts assessed their efficacies. We are still continuing to discuss several pharmaceutical companies to increase the drugs cohorts in this platform. This trial is now recruiting the patients and is contributing significantly to increase the treatment opportunity for the cancer patients. Clinical trial information: jRCTs031190104 .
Predictors of re-admission after COVID-19 hospitalizations in patients with underlying gastrointestinal malignancy.
Authors: Mihir Shah, Rohan Gajjar, Vaishali Deenadayalan, Michelle Ishaya, Rafaella Litvin, Muhammad Bilal Ibrahim, Ayobami Gbenga Olafimihan, Kunnal Batra
Journal: Journal of Clinical Oncology (2023)

e16327 Background: COVID-19 infections have been known to cause worse outcomes in patients with underlying co-morbid conditions. Currently, there is limited data regarding re-admissions in such patients after COVID-19 infection. So, we pursued to assess the rates, predictors, and causes of re-admission after COVID-19 infection in patients who had underlying gastrointestinal malignancy. Methods: The National Readmission Database for 2020 was analyzed to identify patients with COVID-19 hospitalizations who also had a co-diagnosis of GI malignancy. Data for re-admission was gathered, at 30 and 90 days after initial hospitalization. Multivariate logistic and linear regression analysis was used accordingly to adjust for possible confounders. Results: For 30 days: A total of 2,726 COVID-19 hospitalizations had a co-diagnosis of GI malignancy. The mean LOS (length of stay) for index admission was 8.7 days. The mean TOTCHG (total hospital charge) for index admission was $85,747. Within 30 days from discharge, 462 (21%) were re-admitted. The in-hospital mortality in re-admissions (18.4%) was quite similar to that for index hospitalization (18.5%). Positive predictors of re-admission include shorter length of stay during initial hospitalization (&lt;3 days), anemia, renal insufficiency/chronic kidney disease, and atherosclerosis of the aorta. Females had a lower chance of re-admission compared to males. Among the top causes of re-admission were ongoing COVID-19 infection (27%), sepsis (16.3%), acute kidney injury (2.4%), and metabolic encephalopathy (1.2%). For 90 days: A total of 1,782 COVID-19 hospitalizations had a co-diagnosis of GI malignancy. The mean LOS (length of stay) for index admission was 9.2 days. The mean TOTCHG (total hospital charge) for index admission was $90,908. Within 90 days from discharge, 411 (29%) were re-admitted. The in-hospital mortality in readmissions (14%) was lower than that for index hospitalization (20.3%). Predictors of re-admissions include secured insurance, anemia, renal insufficiency/chronic kidney disease, and cerebrovascular accidents. Top causes of re-admission were ongoing COVID-19 infection (18.5%), aspiration pneumonitis (2.9%), pneumonia (2.3%), and acute kidney injury (1.4%). Conclusions: Infections were the leading cause of re-admission, which is an important factor to consider when managing patients with GI malignancies due to sub-optimal immunity. Among these patients, those with concomitant anemia and chronic kidney disease were more prone to being re-admitted. Patients with GI malignancies also tended to have a higher length of stay, leading to higher charges, more exposure to nosocomial infections, and delays in cancer treatment leading to worse cancer outcomes. Pre-mature discharges, without medical optimization, can also potentially predispose to higher rates of re-admissions.
Ultrasensitive detection and monitoring of central nervous system tumors from plasma using personalized whole-genome ctDNA profiling.
Authors: Ivy Tran, Kristyn Galbraith, Sharon L. Gardner, Jeffrey C. Allen, David Harter, Jeffrey Wisoff, Eveline Teresa Hidalgo, Danielle Afterman, Santiago Gonzalez, James Smadbeck, Tomer Lauterman, Ury Alon, Ravi Kandasamy, Iman Tavassoly, Paz Polak, Boris Oklander, Praveen Raju, Asaf Zviran, Matija Snuderl
Journal: Journal of Clinical Oncology (2023)

2064 Background: Patients with the central nervous system (CNS) tumors are largely followed up by imaging. Current plasma-based liquid biopsy techniques have limited utility in neuro-oncology due to a low circulating cell-free tumor DNA (ctDNA) burden, blood-brain barrier, and low number of mutations in coding regions. Whole genome sequencing (WGS)-derived patient specific mutational signature from a matched tumor-normal WGS can provide a personalized, highly sensitive and specific approach to detect mutations in ctDNA and provide blood-based monitoring in brain tumor patients. Furthermore, it can be performed on lower amount of peripheral blood since WGS requires less sequencing depth compared to targeted ctDNA panels. Methods: We have profiled a cohort of 28 extra- and intra-axial adult and pediatric brain tumors including adult and pediatric low- and high-grade glioma (9), meningiomas (11), medulloblastomas (5), ependymomas (2), neurocytoma (1). Tumor DNA was extracted from archival pathology tissue, normal DNA from unsorted white blood cells, and ctDNA from 1-2 mL of post-surgery plasma. WGS was performed with 40x coverage for Tumor-Normal DNA and 20x for ctDNA. Using WGS of matched Tumor-Normal and plasma samples, we derived a personalized mutational pattern using SNVs, indels, and copy numbers for quantification and ultra-sensitive detection of ctDNA in plasma samples. An AI-based error suppression model was implemented to filter out the noise in the cell-free DNA (cfDNA) while the personalized mutational signature was used to detect the ctDNA in the cfDNA and to amplify the somatic signal to determine the Tumor Fraction at the time of diagnosis, during the therapy or surveillance period. The ctDNA Tumor Fraction (TF) was compared to the clinical status and MRI-based imaging. Results: All subtypes of brain tumors contained enough mutations to derive personalized mutational signatures. Most mutations were distributed in the noncoding DNA. TF correlated with clinical status and with the disease course on imaging at given time points reaching a 10 -4 minimal residual disease detection sensitivity. We were able to detect ctDNA across all WHO grades ranging from WHO 1 meningioma to WHO 4 glioblastoma and medulloblastoma. Furthermore, we were able to detect tumor-specific copy number aberrations such as MYCN amplification in plasma samples and mutational signatures. Conclusions: Here we demonstrate that patient-specific WGS tumor signature in ctDNA from plasma can be used for sensitive monitoring of adults and children with primary low- and high-grade CNS tumors.
Real-world safety and effectiveness of CT-P6 (biosimilar trastuzumab): A post-marketing surveillance study in Korea.
Authors: Min-Ho Park, Tea Hyun Kim, Jae Hong Seo, Jung Ho Park, Min-Ki Seong, Keon Uk Park, Min Kyoon Kim, Myungchul Chang, Su-Jin Koh, Moon Hee Lee, Seung Taek Lim, Young Bum Yoo, So Yeon Oh, Sung Hyun Kim, Tae Hong Park, Hana Ju, Eric Hyungseok Baek, Sinhye Kim, Nahyun Kim, Eunkyung Lee
Journal: Journal of Clinical Oncology (2023)

e13025 Background: CT-P6 is a biosimilar trastuzumab product approved in many countries worldwide, including the European Union and the United States. This study aims to confirm the safety and effectiveness of CT-P6 in routine clinical practice settings for the approved indications of HER2-positive metastatic breast cancer (MBC), early breast cancer (EBC), and metastatic gastric cancer (MGC) in the Republic of Korea. Methods: The observational, prospective, multi-center, post-marketing surveillance (PMS) study was conducted from October 5, 2018 to October 4, 2022, on Korean patients diagnosed with MBC, EBC or MGC and newly treated with CT-P6 regardless of previous treatment of trastuzumab products other than CT-P6. Patients receiving at least one CT-P6 treatment according to the prescribing information and being monitored for safety and effectiveness were included in these analyses. Safety was evaluated by all types of adverse events (AEs), including adverse drug reaction (ADR), and serious adverse event (SAE); for up to a year after the first dose of CT-P6. Safety was further summarized by background factors (demographic and clinical characteristics) for subgroup analysis to identify variables independently affecting the incidence proportion. As for effectiveness, disease-specific clinical response (by best overall response for MBC and MGC; disease progression, and pathologic complete response (pCR) for EBC) were assessed for up to one year. Results: The safety population included 642 patients (94 MBC, 494 EBC, 54 MGC). For patients with MBC, AEs occurred in 71.28%, ADRs in 48.94%, and SAEs in 19.15%. For EBC, AEs occurred in 43.52%, ADRs in 26.52%, and SAEs in 6.48%. In case of MGC, AEs occurred at a rate of 79.63%, ADRs at 40.74%, and SAEs at 14.81%. Overall, the incidence of ADR was statistically different for groups ≥65 of age ( p=0.0323); comorbidity or complication, especially with cardiac disorder ( p=0.0018); and previous chemotherapy ( p=0.0002). In terms of effectiveness, positive outcomes were observed. Conclusions: CT-P6 administered to Korean patients according to the prescribing information was well tolerated, with no new safety signals identified. The safety and efficacy profiles of CT-P6 in a real-world population were consistent with those observed in the previous clinical studies. [Table: see text]
Outcomes of stereotactic radiosurgery in central nervous system lymphoma: A single institution experience.
Authors: Farhan Azad, Fatemeh Fekrmandi, Mody Amin, Victor Goulenko, Ahmed Belal, Robert Plunkett, Andrew J. Fabiano, Robert Alan Fenstermaker, Lindsay J. Lipinski, Pallawi Torka, Matthew Joseph Cortese, Francisco J. Hernandez-Ilizaliturri, Dheerendra Prasad
Journal: Journal of Clinical Oncology (2023)

e14061 Background: Primary or systemic high-grade B-cell lymphoma with secondary central nervous system lymphoma (PCNSL or SCNSL) are currently treated with high-dose methotrexate (HD-MTx) based chemo-immunotherapy regimens with/without whole brain radiation therapy (WBRT). CNS relapse can occur in up to 50% of patients with PCNSL or SCNSL. WBRT has been used as a salvage therapy for those patients. However, long-term neurological toxicities significantly reduce its clinical benefit. Stereotactic radiosurgery (SRS) is the administration of a localized, high dose of ionizing radiation. Limited studies exist exploring SRS as a treatment modality in relapsed/refractory (r/r) PCNSL/SCNSL. Methods: We conducted a retrospective single-center study evaluating the clinical efficacy of SRS in r/r PCNSL/SCNSL. Demographic, clinical, pathological, and treatment characteristics were collected in 29 r/r PCNSL (N=17)/SCNSL (N=12) patients, age ≥ 18 years, who received SRS between 01/2000 and 01/2023. Progression-free survival (PFS) and overall survival (OS) were calculated and reported using Kaplan-Meier analyses and log-rank tests. Results: Baseline characteristics are summarized (Table). The median Karnofsky performance status and Charlson comorbidity index were 70 and 5 respectively. For patients with PCNSL (N=17), the most common prior chemotherapy regimen administered was rituximab (R) in combination with the DeAngelis regimen (N=12), followed by the MATRIX regimen (N=3). In patients with SCNSL, the most common systemic chemotherapy regimen used was R + CHOP (N=9). Few patients received temozolomide (N=2). 5/29 (17%) of patients received WBRT before SRS. The overall response rate (ORR) to SRS in r/r PCNSL was 60% (7 CR and 2 PR). The ORR in r/r SCNSL was 83% (7 CR and 3 PR). The median OS of the overall cohort was 7.0 months (95% CI 5.1-8.9), while the median PFS was 5.0 months (95% CI 1.2-8.7). For patients with PCNSL, the median OS was 10.0 months (95% CI 2.2-17.7), and only 7 months (95% CI 1.8-12.1) for patients with SCNSL. Prior WBRT was associated with worse survival outcomes. Of interest, WBRT was avoided in 24/24 patients (100%). Conclusions: Our data support that CNSL patients can benefit from SRS therapy, with acceptable OS and PFS. In addition, the disease control spared patients from WBRT and therefore, mitigated neurological complications associated with that modality. [Table: see text]
The role of ct-DNA in breast cancer surveillance assessing treatment response and recurrence: A community center experience.
Authors: Farhan Khalid, Muhammad Tayyeb, vishakha sirpal, Richi Kashyap, Ahmad Al-alwan, Rajshree Gupta, Vinit Singh, Trishala Meghal
Journal: Journal of Clinical Oncology (2023)

e13021 Background: Breast cancer is a heterogeneous disease and primarily classified on immunohistochemistry. Currently treatment is based on biopsy but studies have showed changes in subtype and acquired resistance in the original subtype due to cancer therapies. While biopsy is gold standard, recently liquid biopsy from serum containing circulating tumor DNA (ct-DNA) has emerged as a noninvasive technique of tumor surveillance. Methods: This is a retrospective study approved by the IRB at Monmouth Medical Center. Objectives were to identify use of ct-DNA level and highlight the trends over course of treatment. Subjects were identified by reviewing patient’s charts and included on criteria of age &gt; 18 years and in whom ct-DNA level was followed up. 27 patients were identified and results were obtained by categorizing the patients and calculating the proportions. Results: A total of 27 patients were included. The mean age at diagnosis of cancer was 56.29 years (95% CI 51.19-61.39). Among 27 patients, 11 had left sided and 16 had right sided tumor. The pathology identified was Invasive ductal in 18, adenocarcinoma in 2, lobular in 4, poorly differentiated in 2 and mesenchymal in 1 of the patients. Hormonal subtypes identified were triple negative in 11, ER/PR+ve/Her 2-ve in 8, triple positive in 2, ER/PR-ve/Her 2+ve in 1 and ER+ve in 5 of the patients. Among 27, 8 of the patients had stage I, 15 had stage II, 3 had stage III and 1 had stage IV disease. During the course of treatment, 7 of patients had left, 10 had right and 7 had bilateral mastectomy due to BRCA mutation identified on genetic testing. 3 of the patients did not undergo surgery. ct-DNA levels were elevated 8.05 and 1.31 MTM/ml in 2 patients and subsequently became undetectable and decrease in tumor size was noticed from 6.1 cm to 1.1 cm and 1.8 cm to 9mm. ct-DNA levels remained undetectable the rest of 25 patients and patient’s remained gross tumor free on interval MRI imaging of the breasts. Conclusions: The ct-DNA levels have a great utility in establishing the correlation of treatment effect on tumor volume. All this information is vital for clinical decision making and appropriate management. Therefore, the application of liquid biopsy and ct-DNA analysis in breast cancer opens a window of opportunity that encompasses all possible disease situations: from early diagnosis, through the detection of minimal residual disease, the early detection of relapse, and the monitoring and treatment planning for advanced disease. A limitation of study was low sample size. [Table: see text]